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Published on: June 17, 2015
Methylphenidate is not clastogenic in cultured human lymphocytes and in the mouse bone-marrow micronucleus test
Willi Suter1, Hans-Joerg Martus, Azeddine Elhajouji
1Safety Assessment and Profiling, Exploratory Development, Novartis Pharma AG, MUT-2881.2.35, CH4002 Basel, Switzerland. willi.suter@novartis.com
Abstract:
Methylphenidate (MPH) is one of the most frequently prescribed drugs for the treatment of attention deficit hyperactivity disorder (ADHD). A report on cytogenetic effects observed in peripheral lymphocytes from children treated for 3 months with MPH raised questions about the genetic toxicity of this compound. A critical review of this data concluded that the cytogenetic effects in treated children remain unexplained. A literature review showed that MPH was found negative in most genetox studies performed, but no in vitro chromosome aberration data in human lymphocytes have been published. Therefore, we conducted a chromosomal aberration study in cultured human peripheral lymphocytes. The results of this investigation showed that d,l-methylphenidate (MPH, Ritalin) in concentrations up to 10 mM did neither induce structural nor numerical chromosome abnormalities. An oral mouse bone-marrow micronucleus test in B6C3F(1) mice, with doses up to 250 mg/kg bw, was negative too. The data of these studies confirm the absence of clastogenic activity of MPH in non-clinical studies.
Insights
Methylphenidate (MPH), a common ADHD treatment, was evaluated for genetic toxicity. Studies confirmed MPH does not cause chromosome damage in human cells or mouse bone marrow, indicating it is not clastogenic.
Area of Science:
- Pharmacology
- Toxicology
- Genetics
Background:
- Methylphenidate (MPH) is a widely prescribed medication for Attention Deficit Hyperactivity Disorder (ADHD).
- Previous reports suggested potential cytogenetic effects of MPH in children, prompting further investigation into its genetic toxicity.
- A critical review indicated that observed cytogenetic effects remained unexplained, and a lack of in vitro human lymphocyte data existed.
Purpose of the Study:
- To investigate the in vitro clastogenic and aneugenic potential of Methylphenidate (MPH) in human lymphocytes.
- To evaluate the in vivo genotoxicity of MPH using a mouse bone-marrow micronucleus test.
- To confirm the absence of genetic toxicity for MPH in non-clinical studies.
Main Methods:
- In vitro chromosomal aberration assay using cultured human peripheral lymphocytes exposed to MPH up to 10 mM.
- In vivo oral mouse bone-marrow micronucleus test in B6C3F(1) mice with doses up to 250 mg/kg body weight.
- Analysis of structural and numerical chromosome abnormalities and micronuclei formation.
Main Results:
- MPH did not induce structural or numerical chromosome abnormalities in human lymphocytes at tested concentrations.
- The in vivo mouse micronucleus test showed negative results, indicating no genotoxic effects.
- These findings collectively demonstrate the absence of clastogenic activity of MPH.
Conclusions:
- Methylphenidate (MPH) does not exhibit clastogenic activity in human lymphocytes in vitro.
- MPH is not genotoxic in vivo based on the mouse bone-marrow micronucleus test.
- The study confirms the safety profile of MPH regarding genetic toxicity in non-clinical settings.
